1-30739818-C-T

Variant names:

• chr1-30739818-C-T
• NM_006762.3:c.378G>A
• LAPTM5 p.Arg126Arg

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_006762.3(LAPTM5):​c.378G>A​(p.Arg126Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,450,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: LAPTM5 NM_006762.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 0 publications found

Genes affected

LAPTM5 (HGNC:29612): (lysosomal protein transmembrane 5) This gene encodes a transmembrane receptor that is associated with lysosomes. The encoded protein, also known as E3 protein, may play a role in hematopoiesis. [provided by RefSeq, Feb 2009]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP7: Synonymous conserved (PhyloP=-1.19 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006762.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAPTM5	NM_006762.3	MANE Select	c.378G>A	p.Arg126Arg	synonymous	Exon 4 of 8	NP_006753.1	Q13571

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAPTM5	ENST00000294507.4	TSL:1 MANE Select	c.378G>A	p.Arg126Arg	synonymous	Exon 4 of 8	ENSP00000294507.3	Q13571
	LAPTM5	ENST00000875065.1		c.411G>A	p.Arg137Arg	synonymous	Exon 4 of 8	ENSP00000545124.1
	LAPTM5	ENST00000875064.1		c.378G>A	p.Arg126Arg	synonymous	Exon 4 of 8	ENSP00000545123.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1450884 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 721166

African (AFR) AF: 0.00 AC: 0 AN: 33060

American (AMR) AF: 0.00 AC: 0 AN: 43268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25808

East Asian (EAS) AF: 0.00 AC: 0 AN: 38894

South Asian (SAS) AF: 0.00 AC: 0 AN: 84558

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53264

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5706

European-Non Finnish (NFE) AF: 9.04e-7 AC: 1 AN: 1106402

Other (OTH) AF: 0.00 AC: 0 AN: 59924

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	7.6
DANN	Benign	0.76
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-31212665;